DESCRIPTION: (Applicant's Abstract) This is a competing renewal application to continue studies of the interactions of cocaine with buprenorphine and other opioids. Buprenorphine, an opioid mixed agonist-antagonist analgesic, reduces cocaine self-administration in preclinical and clinical studies. Other opioids with different profiles of receptor activity also alter cocaine's reinforcing and discriminative stimulus effects. The overall objective of the proposed studies is to clarify the mechanism(s) by which buprenorphine and other opioids reduce cocaine self-administration and modulate its discriminative stimulus effects. Data obtained will suggest new approaches to the clinical treatment of cocaine abuse. The development of more effective pharmacotherapies for the treatment of cocaine abuse and reduction of risk for AIDS has major public health significance and remains one of NIDA's priority concerns. The effects of opioids with selectivity for mu, kappa and delta receptors on the reinforcing and discriminative stimulus effects of cocaine will be studied in well-established primate models. The effects of acute and chronic opioid treatment on cocaine self-administration will be compared with saline-placebo treatment in an own-control, cross-over design. Both cocaine and food self-administration will be examined to assess the relative selectivity of treatment drug effects on cocaine self-administration. This preclinical model of drug self-administration has proved valuable for assessment of potential pharmacotherapies for drug abuse treatment. Treatment with combinations of opioids that have different receptor selectivities and differing effects on dopamine release will also be studied to further analyze the pharmacological determinants of buprenorphine's effects on cocaine self-administration. The proposed studies should contribute to our understanding of the neurobiological bases of cocaine's interactions with mu, kappa and delta opioids and suggest new directions for the development of improved pharmacotherapies. A new model of "relapse" also is proposed to determine whether drugs that reduce cocaine self-administration also are effective in preventing resumption of cocaine self-administration after a period of cocaine abstinence. The proposed relapse model is designed to simulate events in a clinical treatment situation and to compare the effects of abstinence alone and abstinence plus medication treatment on susceptibility to relapse.